The core hypothesis of this proposal is that connexin protein modification and interactions regulate connexin biosynthesis and targeting, gap junctional assembly and degradation, and channel permeability and gating. In addition, as multiple forms of human lens connexins have been identified in patients with congenital cataracts, it is also hypothesized that these mutations lead to impaired intercellular communication due to defects in the regulated processes outlined above. The chicken connexin56 (Cx56) will be studied as a prototype for the function and regulation of fiber connexins. The consequences of phosphorylation of Cx56 will be determined in addition to possible association of Cx56 with other cellular proteins. The genomic structure of the chicken connexin genes will be analyzed to determine elements involved in genetic regulation. The human connexins Cx46 and Cx50 will also be studied in a similar fashion to the chicken genes.